Atlas of Human Assisted Reproductive Technologies Mangala Telang
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1Atlas of Human Assisted Reproductive Technologies2
3Atlas of Human Assisted Reproductive Technologies
Editor Mangala Telang MBBS DGO MD FACOG Senior Fellow of American College of Obstetricians and Gynecologists President of Indian Fertility Society Director Fertility Research and IVF Centre New Delhi
4Published by
Jitendar P Vij
Jaypee Brothers Medical Publishers (P) Ltd
EMCA House, 23/23B Ansari Road, Daryaganj
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Atlas of Human Assisted Reproductive Technologies
© 2007, Mangala Telang
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the editor and the publisher.
First Edition: 2007
9788180619540
Typeset at JPBMP typesetting unit
Printed at Ajanta Offset
5To
My parents
Aie, Dada who gave us all they had and Ananya, the sparkle in my life and the future6
7Contributors
Mangala Telang mbbs dgo md facog
Director, Fertility Research and IVF Centre
New Delhi
Ajit Saxena
ms (delhi), frcs (edin), fics, mnams (urol), dipl. urology (london)
Senior Consultant Urologist and Andrologist,
Indraprastha Apollo Hospitals, New Delhi.
Ashok Khurana mbbs md (radiology)
Clinical Director, Senior Fetustician and
Consultant in Reproductive Imaging
Institute of Fertility Fulfilment and Research
New Delhi
Rupin Shah ms mch (urology)
Consultant Andrologist and Microsurgeon
Lilavati Hospital, Mumbai
Vijay Kulkarni ms
Consultant Andrologist and Microsurgeon
Bhatia Hospital, Mumbai
Narendra Malhotra md ficog ficmch ian donald diploma
Practising Obstetrician and Gynecologist
Malhotra Test Tube Baby Centre, Agra
Arun Tewari md
Urologist
Malhotra Test Tube Baby Centre, Agra
Jaideep Malhotra md
Malhotra Test Tube Baby Centre, Agra
Ashok Sharma
Malhotra Test Tube Baby Centre, Agra
Hrishikesh Pai md fcps ficog
Lilavati Hospital IVF Centre, Mumbai and
Batra Hospital IVF Centre, Delhi
Shilpa Shah md dnb fcps
Lilavati Hospital IVF Centre, Mumbai
Rishma Pai md fcps dnb ficog
Lilavati Hospital IVF Centre
Mumbai and Jaslok Hospital
Mumbai
Nandita Palshetkar md fcps ficog
Lilavati Hospital IVF Centre, Mumbai and Batra
Hospital IVF Centre, Delhi
Sushma Ved md
Southend Rotunda (Centre for Human Reproduction), Holy Angels Hospital, Vasant Vihar
New Delhi
Sonia Malik md
Southend Rotunda (Centre for Human Reproduction), Holy Angels Hospital, Vasant Vihar
New Delhi
Sapna Srinivas md
Embryologist, Infertility Institute and Research
Centre, Secunderabad, Andhra Pradesh
Alok Teotia mvsc
Consultant Reproductive Biologist, Indraprastha
Apollo Hospitals, New Delhi
Sudesh A Kamat msc
Consultant Reproductive Biologist, Leelavati Hospital
Mumbai
Vijay Mangoli msc
Reproductive Biologist, Fertility Clinic and IVF
Centre, Mumbai
Ranjana Mangoli msc
Reproductive Biologist, Fertility Clinic and IVF
Centre, Mumbai8
Col RK Sharma md
Senior Advisor (Obs., Gynae & ART)
Army Hospital (Research & Referal)
New Delhi
Prochi Madon
Department of Assisted Reproduction and Genetics
Jaslok Hospital and Research Centre
Mumbai
Arundhati Athalye
Department of Assisted Reproduction and Genetics
Jaslok Hospital and Research Centre
Mumbai
Nandkishor Naik
Department of Assisted Reproduction and Genetics
Jaslok Hospital and Research Centre
Mumbai
Firuza Parikh md
Department of Assisted Reproduction and Genetics
Jaslok Hospital and Research Centre
Mumbai
H Ingolf Nielsen
MediCult a/s, Møllehaven 12, DK-4040 Jyllinge
Denmark, and Essex Fertility Centre
United Kingdom
Anne Lis Mikkelsen
The Fertility Clinic, Herlev University Hospital
DK-2730 Herlev, Denmark
NS Moorthy
Medical Director, Asia Cryo-Cell Private Limited
Chennai
GA Rama Raju
Krishna IVF Clinic, Visakhapatnam
K Murali Krishna
Krishna IVF Clinic, Visakhapatnam
G Jaya Prakash
Krishna IVF Clinic, Visakhapatnam
K Madan
Krishna IVF Clinic, Visakhapatnam
9Foreword
The birth of the first human baby conceived in vitro, in July 1978, was not an accident. It was preceded by more than 30 years of intense laboratory and animal experimentation by innumerable scientists. From this long list, I believe that it is imperative to highlight: R Moricard, CR Austin, MC Chang, L Dauzier, C Thibault, JM Bedford, R Yanagimachi, P Soupart, BD Bavister and RG Edwards.
Dauzier and Thibault of France were the first to report on “Fertilization in vitro of rabbit oocyte” in 1954. Chang and Bedford confirmed their findings in 1959, following which Yanagimachi and Chang reported on “Fertilization of hamster eggs in vitro” in 1963. Two years later Edwards reported the “Maturation in vitro of mouse, sheep, cow, pig, rhesus monkey and human ovarian oocytes.” The first clinician, Patrick Steptoe, entered the scene in 1968 when he started to collaborate with Edwards; this association enabled them to perform important studies using human gametes: “Early stages of fertilization in vitro of human oocytes matured in vitro” (1969), “Fertilization and cleavage in vitro of preovulatory human oocytes” (1970), and “Human blastocysts grown in culture” (1971).
The vision and driving force behind the human work was Bob Edwards. The first human pregnancy derived from in vitro fertilization (IVF) was a tubal pregnancy in 1976. The first baby conceived in vitro was born, by cesarean section, on July 25, 1978, just before midnight. Both events were reported by Steptoe and Edwards in the Lancet; the birth of the first IVF baby was reported immediately and with great fanfare by the world media.
During the first decade that followed this event, the IVF results remained fairly modest. The first international survey carried out in 1984 by Markku Seppala reported a delivery rate per initiated cycle of only 5.4%. This rate remained under 12% until the end of the decade. My team and I, in Vancouver, were fortunate to have the first baby conceived in vitro in Canada; he was born on December 25, 1983.
The nineties brought sunshine to IVF; the success rate improved gradually, and by the end of the decade the rate of delivery per initiated cycle, in the USA, reached 25.4%. In 2003, the last reported year, this rate was 28%. It is interesting to note that improvement in outcomes was realized without any change in the cancellation rate, which remained around 13 to 14%.
Intracytoplasmic sperm injection (ICSI) also started with animal experimentation by Gianpiero Palermo and co-workers. Their initial report in 1991 “Enhancement of acrosome reaction and subzonal insemination of a single spermatozoon in mouse eggs” was followed by work on human oocytes that led to a report in 1992 “Induction of acrosome reaction in human spermatozoa used for subzonal insemination”. During the same year, Palermo and associates were also able to report on pregnancies in human subjects: “Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte”.
The introduction of ICSI has dramatically changed treatment of male infertility. The 2003 USA results clearly confirm the results of previous years, that the delivery per oocyte pick-up (OPU) rates are fairly similar between couples with male factor and those without male factor treated with IVF plus ICSI.10
The significant improvement in outcomes was due to the simplification of clinical and especially the simplification and standardization of laboratory techniques; the improvements in cryopreservation of supernumerary embryos, the advent of intracytoplasmic sperm injection (ICSI), and to the industrialization of IVF services. This improvement came about at the expense of a very high rate of multiple pregnancies, especially triplets and higher order of multiples, as a result of replacement (transfer) of multiple embryos.
Multiple pregnancies are associated with a higher incidence of obstetrical complications and neonatal complications and deaths. They incur significant costs to the society, associated with the care of premature and sick infants, and tax the parents financially and emotionally. Fortunately, there is now a growing movement to decrease the number of embryos transferred, and to individualize the number taking into account the woman's age the quality of available embryos and other pertinent parameters.
Assisted Reproductive Technology (ART) which includes IVF has had a tremendous impact in the practice of reproductive medicine. It made IVF possible for a significant proportion of women, who otherwise would not achieve a pregnancy, to bear children. It has permitted the introduction of prenatal genetic diagnosis (PGD), enabling couples who are carriers of genetic disease to have healthy children.
We must be reminded that, despite the impressive progress in outcomes, ART fails to yield an offspring for approximately 50% of couples willing to undergo 3 cycles of treatment. And many do not persist that long. The industrialization of IVF proved to be a two edged sword. On the one hand, it has permitted ready access to this form of treatment globally, while on the other it funnels to IVF many couples who would benefit from simpler forms of treatment. It has caused significant reduction in the use and teaching of reproductive microsurgery. The reestablishment of a balanced approach remains the responsibility of the teaching institutions.
The selection of the initial and subsequent treatment modalities, for a given infertile couple, must be individualized on the basis of the findings obtained from a proper investigation. Reconstructive surgery and ART must not be viewed as competitive techniques; instead, they should be accepted and used as complementary methods to achieve a greater rate of success in patients presenting with complex fertility problems. There is ample evidence in this regard.
IVF has also opened many areas of investigation and progress: stem cell research, gene therapy, therapeutic cloning, etc. It is also opening the Pandora box of human cloning. Such is the destiny of scientific research.
Progress is made by visionaries who are willing to push the envelope; visionaries who have the will to stay the course, and the strength to withstand the abuse from those who fear change.
I am honored to be asked to contribute a foreword to this “Atlas of Human Assisted Reproductive Technologies” edited by Dr. Mangala Telang. This is a concise, practical and richly illustrated book, designed for those involved in the practice of ART, and the personnel working in ART laboratories.
The book is divided into three sections: clinical aspects of ART, laboratory aspects of ART, and new developments. The initial chapter of the first section is authored by Dr. Telang and devoted to the female partner. The chapter commences with a detailed discussion of the evaluation of the female partner, which is so important in selecting the most appropriate treatment. The second part of the chapter covers important clinical aspects of assisted reproduction including controlled ovarian stimulation, ovum pick-up and transfer, etc. The subsequent four chapters that complete the first section ably discuss the evaluation of the male partner, non-surgical and surgical methods of sperm collection, and the role of ultrasound in ART.
The second section commences with a chapter that discusses the laboratory, its equipment, quality control and assurance. The subsequent seven chapters in this section provide a detailed description of the various laboratory 11techniques: sperm preparation, culture, ICSI, cryopreservation, PGD, etc. The last section, “new developments” include three chapters devoted to in vitro maturation, stem cells, and vitrification.
The balance and clarity of the book reflects the expertise and wisdom of its editor Dr. Mangala Telang who selected its authorship, and crafted and edited its contents. I am certain that it will prove to be a very useful guide to those involved in the practice of ART, personnel working in ART laboratories, and undoubtedly residents in gynecology.
Professor Victor Gomel
Department of Obstetrics and Gynecology
Faculty of Medicine, University of British Columbia
Vancouver BC. Canada12
13Preface
Assisted Reproductive Technologies (ART) have given a ray of hope to the countless couples who otherwise had no possibility of fulfilling their dream of parenthood. There is hope for women who have lost ovarian function, whose fallopian tubes are blocked, who do not have healthy wombs and even those who develop cancer of the reproductive organs. There is also hope for men who for some reason produce very few sperms or none at all. There is constant addition to the armamentarium needed for ovulation induction and laboratory equipment and techniques.
There was no atlas in the Indian market which would explain pictorially all the facets of clinical and laboratory management of ART. The atlases available from outside India were very expensive for Indian laboratories and this is an attempt to make such a book available for all ART laboratories. All the authors are very renowned and experienced in their own fields of expertise which they have shared in this atlas.
There is a comprehensive section on clinical aspects, which describes in detail the evaluation of an infertile woman and the management of various problems which could affect her fertility.
There are chapters which handle male infertility comprehensively.
Apart from the routine ART, latest advances in cryopreservation, in vitro maturation, vitrification have been contributed by very experienced scientists. The latest interest in stem cell research has also been addressed.
I hope this atlas finds a place in every IVF laboratory and is found to be useful both by the clinician and the laboratory personnel.
Mangala Telang
14Acknowledgements
I am very thankful to Dr Victor Gomel who is a pioneer in the field of endoscopy and ART for being gracious and for writing the foreword for this atlas.
I am grateful to all the contributors for making special efforts to make their text meaningful by adding their personal experiences in the form of pictures.
I am thankful to Sudesh A Kamat for helping me to contact contributors from various parts of the country.
My special thanks to Dr Ashok Khurana and Dr Narendra Malhotra for lending some of their pictures.
I have to acknowledge the valuable help given by Vishal Mittal with the computer work.
Last but not the least I have to thank my husband Dinbandhu for his understanding and encouragement always and Nandita and Sucheta for being bare for me.
Shri Jitendar P Vij gave me the idea to bring out an atlas and I thank him and Jaypee Brothers Medical Publishers for the excellent work they have done with the editing and printing.